U.S. Pat. No. 4,547,371 describes substituted cephalosporins containing sulfone moieties as potent elastase inhibitors which are useful anti-inflammatory/anti-degenerative agents. Copending U.S patent application Ser. No. 930,193, filed Nov. 12, 1986 now abandoned also describes substituted cephalosporin sulfones as antiinflammatory and antidegenerative agents.
The compounds of this type are generally prepared from t-butyl 3-acetyloxymethyl-7.beta.-amino-8-oxo-5-thia-l-azabicyclo [4.2.0]oct-2-ene-2-carboxylate (the t-butyl ester of 7-ACA) which is converted into the 7.alpha.-alkyoxy derivative via diazotization and displacement. It is this 7.alpha.-alkoxy derivative which is then oxidized to cephalosporins containing sulfone moieties. The procedure employed in Copending U.S patent application Ser. No. 930,193, filed Nov. 12, 1986 now abandoned involves the diazotization of 7-ACA t-butyl ester with p-toluenesulfonic acid/sodium nitrite in a biphasic methylene chloride/water system, followed by the rhodium acetate-catalyzed reaction with methanol to obtain, about 20-30% of the desired 7.alpha.-methoxy insertion product.